Causally Interpretable Meta-analysis: Application in Adolescent HIV Prevention.

Endowing meta-analytic results with a causal interpretation is challenging when there are differences in the distribution of effect modifiers among the populations underlying the included trials and the target population where the results of the meta-analysis will be applied. Recent work on transportability methods has described identifiability conditions under which the collection of randomized trials in a meta-analysis can be used to draw causal inferences about the target population. When the conditions hold, the methods enable estimation of causal quantities such as the average treatment effect and conditional average treatment effect in target populations that differ from the populations underlying the trial samples. The methods also facilitate comparison of treatments not directly compared in a head-to-head trial and assessment of comparative effectiveness within subgroups of the target population. We briefly describe these methods and present a worked example using individual participant data from three HIV prevention trials among adolescents in mental health care. We describe practical challenges in defining the target population, obtaining individual participant data from included trials and a sample of the target population, and addressing systematic missing data across datasets. When fully realized, methods for causally interpretable meta-analysis can provide decision-makers valid estimates of how treatments will work in target populations of substantive interest as well as in subgroups of these populations.